This proposal is submitted to a request for applications to develop small animal models to screen antiepileptic drugs (AED). It involves defining ways to quickly, easily, and reliably study drugs in rats for their efficacy against partial (focal) seizures using rapidly recurring seizures triggered with electrical stimulation through stereotactically implanted intracerebral electrodes. Our work so far has been with seizures originating in the hippocampus as a model of complex partial seizures and has defined procedures that provide serial, stable and stereotyped epileptic responses at a rate of once every 30 minutes. Three test protocols have been established to gauge AED effects. These protocols concurrently measure three parameters that examine separate aspects of epileptogenicity, including seizure initiation, seizure prolongation, and seizure spread. Studies with known, prototypic AED have established way to quantitatively assess dose-response, time- action, and relative potency characteristics of AED. These features of the system make it ideal to define pharmacokinetic and pharmacodynamic properties of potential new AED. The proposed studies will answer 5 questions: 1) How can the system be modified to more rapidly and efficiently screen AED? 2) How can the system be modified to test drugs for action against focal epileptogenesis in limbic centers? 3) How do novel AED behave in the testing procedures? 4) How can the basic test procedures be modified to screen for drugs effective against simple partial seizures and against seizure generalization? 5) How can the test procedure be modified to test AED against spontaneous seizures? As a result of the proposed studies, a flexible and powerful screening system for AED will be available that can examine various aspects of different types of seizures and that can provide comprehensive quantitative analyses of drugs in a highly efficient manner. With this system, bringing new compounds from the chemist's laboratory to clinical trial will be facilitated.